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The use of stimulants as a fatigue countermeasure in military aviation has a long history dating back to British use of amphetamines during World War II. The issue of US pilots taking psychologically active controlled substances to counteract the effects of fatigue recently ignited a public debate following the Tarnak Farms friendly fire incident. Supporters of using stimulants in this setting maintain that fatigue induced performance degradation poses a much greater risk to pilot and aircraft safety than risks associated with stimulant medications. Conversely, opponents contend that these agents alter judgment and decision-making ability in aviators who have at their disposal an instrument with a degree of precision and lethality never before seen in the history of conventional warfare. This review represents an effort to inform the military community about the dangers of fatigue in the aviation setting along with the appropriate role of stimulants in attenuating this danger. Based on detailed analysis of existing research in the field of aviation fatigue management, along with considerations of various cognitive processes and the possible effects of stimulant medications on those processes, several concluding recommendations directed to Air Force commanders, senior leaders, policy makers, and aircrew will help guide future fatigue management measures and policies.